Liver Disease Flashcards
What are the important functions of the liver?
It is the major focus of synthetic, catabolic, and detoxifying activities in the body:
Metabolism of all food as well as some drugs (CYP450 enzymes)
Excretion of heme pigments
Important participant in immune response
Synthesis and storage of clotting factors (I, II, V, VII, IX, and X) vitK dependent factors are II, VII, IX, and X.
Why should dentists care about the liver function?
LA, analgesics, sedative, antibiotics, and antifungals are all metabolized in the liver.
What is hepatitis?
Liver inflammation
What causes hepatitis?
Infections or other causes:
Infectious causes = HAV, HBV, HCV, HDV, HEV, infectious mononucleosis, secondary syphillis, and tubercolosis.
Other causes = Excessive use of toxic substances inlcuding paracetamol, halothane, ketoconazole, methyldopa, methotrexate, and carbamezapine. Alcohol.
What causes most cases of hepatitis viral infections?
HAV, HBV, HCV. HAV is less common now due to more hygienic conditions.
HBV and HCV infections affect 540 million people worldwide. 370 million HBV and 170 million HCV. Causes considerable morbidity via cancer and cirrhosis.
How common is acute hepatitis?
Acute hepatitis affects approx 1% of people in the US with 80k new cases every year
How common is death from viral hepatitis?
Approximately 1 million deaths each year are caused by viral hepatitis
How are hepatitis A and E spread?
Most commonly via faecal oral route.
Occur in outbreaks as well as sporadically
Generally self limiting
What causes non-(A-E) hepatitis?
Unknown viral aetiology
How does hepatitis B, C, and D spread?
Parenteral routes most commonly and less commonly by intimate or sexual exposure.
Does not cause outbreak and can become chronic
How does viral hepatitis happen?
The virus is not directly cytopathic. Indirect damage occurs due to immune response by cytotoxic T-cell responses. Pro-inflammatory cytokines are involved as well as NK cells and antibody dependent cellular cytotoxicity.
Antibodies can provide partial immunity to reinfection
What is the clinical presentation of viral hepatitis?
Highly variable course: Transient, asymptomatic infection to severe or fulminant disease. Can be self-limited with complete resolution, relapsing, or chronic infection.
4 phases: Incubation, preicteric, icteric, and convalescence phase.
What is the incubation period in viral hepatitis?
Ranges from 2 to 20 weeks based on viral aetiologic agent and dose.
What are the potential complications of viral hepatitis?
Can be chronic or fulminant.
What happens during the incubation phase of viral hepatitis?
This is determined by the viral etiological agent and exposure dose.
The virus becomes detectable in the blood.
Antibody remains negative
The body has normal serum aminotransferase and bilirubin levels.
What happens during the preicteric phase?
Nonspecific symptoms: Fatigue, nausea, poor appetite, and vague upper right quadrant pain. Lasts 3 - 10 days.
During this phase virus specific antibodies are detectable.
Serum aminotransferase start to increase and viral load are highest in this phase
What happens durng the icteric phase?
Symptoms like jaundice, fatigue, and nausea worsen, hepato/splenomegaly in severe cases
Urine starts to darken in this stage.
Serum bilirubin levels are high
Aminotransferase enzymes are higher.
Viral load begins to lower.
Anorexia and weight loss common at this stage.
What happens during convalescence?
Can be prolonged
Neutralizing antibodies are highest at this stage.
What are the complications of acute viral hepititis?
Hepatic failure
1 - 2% of patients with symptomatic acute hepatitis. HBV > HCV
What are the complications of chronic hepatitis?
Illness of at least 6 months duration.
This develops in 2 - 7% of adults with hepB and 50 - 85% of adults with hepC
What are the signs of poor prognosis in hepatitis?
Persistently worsening jaundice, ascitis, decreased liver size, and higher thrombin time
How is viral hepatitis diagnosed?
hepA: IgM anti-HAV
hepB: HBsAg, IgM anti-HBc
hepC: anti-HCV by EIA
hepD: HBsAg
hepE: History
Mononucleosis: History, WBC, differential counts
Drug-induced hepatitis: History
How does alcoholic liver disease occur?
Alcohol is directly hepatotoxic and indirectly via acetyl aldehyde (which is fibrinogenic) and via cytokines.
How do cytokines lead to alcohoic liver disease?
Alcohol induced influx of endotoxin (LPS) from gut into portal circulation leading to kuppfer cells -> Enhanced chemokine release -> damage to liver hepatocytes
How much alcohol is enough to cause damage?
1 pint (~500ml) of whiskey for 10 years daily or several quarts of wine (1L)
What deleterious effects does alcohol have on the body?
Neural development
Corticotropin releasing hormone system is negatively impacted by alcohol
Metabolism of neutrotransmitters
The function of neurotransmitter receptors
What are the disease outcomes of long term alcohol consumption?
Impairment of the acetylcholine and dopaminergic systems leading to:
Sensory and motor disturbances (e.g., peripheral neuropathies)
Malnutrition (folic acid deficiency)
Anemias
Decreased immune function
Increased mortality rates
Hepatocellular carcinoma
Metastasis to liver
What are the stages of alcoholic liver disease?
Fatty liver: Characterized by presence of fatty infiltrate, after only a moderate use of alcohol for a brief time. This is completely reversible
Alcoholic hepatitis: This is a diffuse inflammatory condition of the liver leading to destructive, irreversible cellular changes, this is reversible overall for the most part but can become irreversible.
Cirrhosis: This is irreversible, characterized by progressive fibrosis and abnormal regeneration of liver architecture resulting in progressive deterioration of liver function and then hepatic failure
What are the features of hepatic failure?
Hepatic failure is characterized by oesophagitis, gastritis and pancreatitis leading to malnutrition, weight loss, protein deficiency, impaired coagulation, endocrine disturbances, jaundice, portal hypertension, oesophageal varices, increased ammonia production leading to encephalopathy, dementia, and psychosis,
This is in addition to cerebral degeneration upper gi tract cancer and liver cancer from heavy alcohol consumption.
What is the clinical presentation of alcoholic liver disease?
Fatty liver: Possible enlargement.
Alcoholic hepatitis:
Nonspecific:
Nausea
Vomiting
Anorexia
Malaise
Weight loss
Fever
Specific:
Hepatomegaly
Splenomegaly
Jaundice
Ascites
Ankle oedema
Spider angiomas
What are the symptoms early stage of alcoholic cirrhosis?
Can be asymptomatic until late stage.
Ascites
Spider angiomas
Ankle oedema
Jaundice
Haemorrhage from oesophageal varices
What are the later signs of cirrhosis?
Hepatic encephalopathy
Coma
Death
What are the nonspecific signs of cirrhosis?
Anaemia
Purpura
Ecchymosis
Gingival bleeding
Palmar erythema
Nail changes
Parotid gland enlargement
What are the lab tests used for diagnosis of alcoholic liver disease?
Elevated bilirubin, alkaline phosphatase, AST, ALT, GGT, Amylase, Uric acid, and cholesterol.
Leukopenia or leucocytosis
Anaemia
Thrombocytopaenia
Carbohydrate deficient transferrin test
What does the AST to ALT ratio tell us about alcoholic liver disease?
AST to ALT ratio above 2 is 90% predictive of alcoholic liver disease.
What does GGT and corpuscular volume tell us about alcoholism?
GGT elevation and mean corpuscular volume are suggestive of alcoholism
What does the carbohydrate deficient transferrin test tell us?
Monitor clniical status of alcohol dependency.
What does thrombocytopaenia tell us about alcoholic liver disease?
Deficiencies of clotting factors can be told by prolonged PT and APTT
How long will improvement take after ceasing alcohol consumption?
18 months there is improvement
How should liver transplant patients be managed?
Pre-transplant dental care: dental clearance
Post transplant management: Multidisciplinary care, maintain oral hygiene and dental care, immunosuppression
How long does liver damage take to progress to cirrhosis?
Median time is 30 years
Can take 5 - 50 years to develop
How does liver damage accumulate?
Chronic injury leads to Inflammatory damage, matrix deposition, parenchymal cell death, angeiogenesis
This leads to disrupted archtecture, loss of function, and aberrant hepatocyte regeneration, eventually leading to cirrhosis
How can accumulated damage of the liver be reversed?
Removal of the underlying cause and anti-fibrotic drug/cell therapy
What are ALT, AST, GGT, and ALP used for?
They are markers of the disease and indicate the severity of hepatocellular damage
What do albumin, bilirubin, and PT/INR indicate?
They are indicators of liver function
How should patietns with alcoholic liver disease be managed?
Understand the possibilty of bleeding and infection. Consider
No need for abx prophylaxis. Avoid abx with liver metabolism
LA: Some are metabolised by the liver
Sedatives: Some are metabolised by the liver
Analgesics: Some are metabolised by the liver
Which LAs are metabolised by the liver?
Lidocaine
Mepivacaine
Prilocaine
Bupivacaine
Which analgesics are metabolised by the liver?
aspirin, paracetamol, codeine, ibuprofen, and meperidine
Which sedatives are metabolised by the liver?
Diazepam
Barbiturates
Which antibiotics are metabolized by the liver?
Ampicillin
Tetracycline
Metronidazole
Vancomycin
What risks should be considered with alcoholic liver disease?
Safe dental care
Potential medical emergencies
Prescribing
Infection control
Impact on oral health
Consider referring
